title: Differences in the expression and sensitivity of cultured rat brain neuronal and glial cells toward the monocrotophos.
abstract: Inducible expressions cytochrome P450s (CYPs) against environmental chemicals in brain tissues of experimental animals is well-documented. However, the precise role of specific brain cell type in the metabolism of different class of xenobiotics has not been explored adequately. We study the expression of selected CYPs (1A1/1A2, 2B1/2B2, 2E1) in primary cultures of rat brain neuronal and glial cell exposed to an organophosphate pesticide-monocrotophos (MCP), a known neurotoxicant. The cultured neurons and glial cells express significant expression of CYP1A1, 2B2 and 2E1 isoenzymes, where the levels were comparatively higher in neuronal cells. Neuronal cells exhibited greater induction of CYP2E1 against MCP exposure, while glial cells were having more vulnerability for CYP1A and 2B isoenzymes. Similarly, cells were showing substrate specific responses against the specific inducers of CYPs, that is, ethanol (2E1), cyclophosphamide (2B1/2B2), 3-methylcholanthrene (1A1/1A2). The altered expression and activity of selected CYPs in cultured neuronal and glial cells could be helpful in explaining the association between MCP-induced neurotoxicity/metabolism and synthesis or transport of the neurotransmitters. The induction of CYPs in glial cells may also have significance as these cells are thought to be involved in protecting the neurons from environmental insults and safeguard them from toxicity. The differential expression pattern of CYPs in neuronal and glial cells exposed to MCP also indicate the selective sensitivity of these cells against the xenobiotics, hence suggested their suitability as tool to screen neurotoxicity potential of variety of xenobiotics.
authors.affiliation: CSIR-Indian Institute of Toxicology Research, Integral University, Lucknow, Uttar Pradesh, India ; Department of Biotechnology, Integral University, Lucknow, Uttar Pradesh, India.
authors.forename: Vinay Kumar
authors.initials: VK
authors.lastname: Tripathi
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
authors.forename: Abhishek Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Mahendra Pratap
authors.initials: MP
authors.lastname: Kashyap
authors.forename: Sadaf
authors.initials: S
authors.lastname: Jahan
authors.forename: Dipak
authors.initials: D
authors.lastname: Kumar
authors.forename: Mohtashim
authors.initials: M
authors.lastname: Lohani
keywords: Cytochrome P450s; Xenobiotic metabolism; monocrotophos; primary culture; rat brain glial cells; rat brain neuronal cells